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Human and mouse type I natural killer T cell antigen receptors exhibit different fine specificities for CD1d-antigen complex.

Wun KS, Ross F, Patel O, Besra GS, Porcelli SA, Richardson SK, Keshipeddy S, Howell AR, Godfrey DI, Rossjohn J
J Biol Chem 287 39139-48 (2012)
Cited: 29 times
EuropePMC logo PMID: 22995911

Abstract

Human and mouse type I natural killer T (NKT) cells respond to a variety of CD1d-restricted glycolipid antigens (Ags), with their NKT cell antigen receptors (NKT TCRs) exhibiting reciprocal cross-species reactivity that is underpinned by a conserved NKT TCR-CD1d-Ag docking mode. Within this common docking footprint, the NKT TCR recognizes, to varying degrees of affinity, a range of Ags. Presently, it is unclear whether the human NKT TCRs will mirror the generalities underpinning the fine specificity of the mouse NKT TCR-CD1d-Ag interaction. Here, we assessed human NKT TCR recognition against altered glycolipid ligands of α-galactosylceramide (α-GalCer) and have determined the structures of a human NKT TCR in complex with CD1d-4',4″-deoxy-α-GalCer and CD1d-α-GalCer with a shorter, di-unsaturated acyl chain (C20:2). Altered glycolipid ligands with acyl chain modifications did not affect the affinity of the human NKT TCR-CD1d-Ag interaction. Surprisingly, human NKT TCR recognition is more tolerant to modifications at the 4'-OH position in comparison with the 3'-OH position of α-GalCer, which contrasts the fine specificity of the mouse NKT TCR-CD1d-Ag recognition (4'-OH > 3'-OH). The fine specificity differences between human and mouse NKT TCRs was attributable to differing interactions between the respective complementarity-determining region 1α loops and the Ag. Accordingly, germline encoded fine-specificity differences underpin human and mouse type I NKT TCR interactions, which is an important consideration for therapeutic development and NKT cell physiology.

Articles - 3vwj mentioned but not cited (2)

  1. Human and mouse type I natural killer T cell antigen receptors exhibit different fine specificities for CD1d-antigen complex. Wun KS, Ross F, Patel O, Besra GS, Porcelli SA, Richardson SK, Keshipeddy S, Howell AR, Godfrey DI, Rossjohn J. J Biol Chem 287 39139-39148 (2012)
  2. The Hypervariable Loops of Free TCRs Sample Multiple Distinct Metastable Conformations in Solution. Crooks JE, Boughter CT, Scott LR, Adams EJ. Front Mol Biosci 5 95 (2018)


Reviews citing this publication (16)

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Articles citing this publication (11)

  1. Guidelines for the use of flow cytometry and cell sorting in immunological studies (second edition). 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  7. Lipid and Carbohydrate Modifications of α-Galactosylceramide Differently Influence Mouse and Human Type I Natural Killer T Cell Activation. Birkholz A, Nemčovič M, Yu ED, Girardi E, Wang J, Khurana A, Pauwels N, Farber E, Chitale S, Franck RW, Tsuji M, Howell A, Van Calenbergh S, Kronenberg M, Zajonc DM. J Biol Chem 290 17206-17217 (2015)
  8. 4"-O-Alkylated α-Galactosylceramide Analogues as iNKT-Cell Antigens: Synthetic, Biological, and Structural Studies. Janssens J, Bitra A, Wang J, Decruy T, Venken K, van der Eycken J, Elewaut D, Zajonc DM, van Calenbergh S. ChemMedChem 14 147-168 (2019)
  9. Novel thioglycoside analogs of α-galactosylceramide stimulate cytotoxicity and preferential Th1 cytokine production by human invariant natural killer T cells. Melo AM, Zhang L, Dockry ÉF, Petrasca A, Ghnewa YG, Breen EP, Morrissey ME, O'Reilly C, Bruen R, O'Meara A, Lysaght J, Zhu X, Doherty DG. Glycobiology 28 512-521 (2018)
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  11. Mouse mucosal-associated invariant T cell receptor recognition of MR1 presenting the vitamin B metabolite, 5-(2-oxopropylideneamino)-6-d-ribitylaminouracil. Ciacchi L, Mak JYW, Le JP, Fairlie DP, McCluskey J, Corbett AJ, Rossjohn J, Awad W. J Biol Chem 300 107229 (2024)


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